Premium
Acid‐sensing ion channels in neurones of the rat suprachiasmatic nucleus
Author(s) -
Chen ChunHao,
Hsu YiTing,
Chen ChihCheng,
Huang RongChi
Publication year - 2009
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2008.166918
Subject(s) - acid sensing ion channel , chemistry , extracellular , suprachiasmatic nucleus , biophysics , amiloride , electrophysiology , nucleus , slice preparation , medicine , endocrinology , ion channel , neuroscience , central nervous system , biochemistry , biology , in vitro , sodium , receptor , organic chemistry
We used reduced slice reparations to study ASIC‐like currents in the rat central clock suprachiasmatic nucleus (SCN). In reduced SCN preparations, a drop of extracellular pH evoked a desensitizing inward current to excite SCN neurones to fire at higher rates. Under voltage‐clamped conditions, all SCN neurones responded to a 5 s pH step to 6.4 with an inward current that decayed with an average time constant of 1.2 s to 10% of the peak at the end of step. The current was blocked by amiloride with an IC 50 of 14 μ m and was carried mainly by Na + , suggesting an origin of ASIC‐like channels. The SCN neurones were sensitive to neutral pH, with 94% of cells responding to pH 7.0 with an inward current. The study of sensitivity to pH between 7.0 and 4.4 revealed a two‐component dose‐dependent H + activation in most SCN neurones, with the first component (85% in amplitude) having a pH 50 of 6.6, and the second (15%) a pH 50 of 5. The ASIC‐like currents were potentiated by lactate and low Ca 2+ , but were inhibited by Zn 2+ . RT‐PCR analysis demonstrated the presence of mRNA for ASIC1a, 2a, 2b, and 3 in SCN. Compared to other central neurones, the unique presence of ASIC3 along with ASIC1a in SCN neurones may contribute to the high pH sensitivity and unusual inhibition by Zn 2+ . The high pH sensitivity suggests that the SCN neurones are susceptive to extracellular acidification of physiological origins and that the ASIC current might play a role in regulating SCN excitability.